Altered kidney matrix gene expression in early stages of experimental diabetes

K. Wu, S. Setty, S. M. Mauer, P. Killen, H. Nagase, A. F. Michael, E. C. Tsilibary

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The expression of mRNA and distribution of α1(IV), α3(IV) chains of type IV collagen, matrix metalloproteinase 2 (MMP-2), and tissue inhibitor of metallo-proteinase 1 (TIMP-1) were examined in kidneys from streptozotocin-diabetic rats, 2.5 months after administration of the drug, an early time point when specific diabetic glomerular changes were still minimal. Ten age-matched Sprague-Dawley rats were assigned to control and diabetic groups. Compared to the controls, the diabetic rats had a significantly lower body weight, higher kidney weight and serum glucose levels, but no significant changes of glomerular surface area and urine albumin were observed. Northern blot analysis, using whole kidney mRNA, revealed that diabetic rat kidneys expressed 113.5% more α1(IV), 46.5% more α3(IV), 54.8% less MMP-2 and 246% more TIMP-1 (in all instances: p < 0.05). These results were corroborated by in situ hybridization for RNA expression. A quantitative analysis of the data indicated the following changes in glomeruli: (1) 74.6% more α1(IV), (2) 103.8% more α3(IV), (3) 40.7% less MMP-2 and (4) 80.9% more TIMP-1. Similar changes were observed in tubular (proximal and distal) cells. We conclude that an increased synthesis and decreased degradation of renal extracellular matrix components occur early after induction of experimental diabetes, before the onset of typical structural changes in the kidneys, and represent changes of specific gene expression at the transcriptional level. All the cell types in the glomerulus as well as the proximal and distal tubules appear to be involved in this alteration of expression, and this is a novel finding.

Original languageEnglish (US)
Pages (from-to)155-165
Number of pages11
JournalCells Tissues Organs
Volume158
Issue number3
DOIs
StatePublished - Jan 1 1997

Fingerprint

Kidney
Gene Expression
Matrix Metalloproteinase 2
Peptide Hydrolases
Messenger RNA
Matrix Metalloproteinase Inhibitors
Collagen Type IV
Streptozocin
Northern Blotting
In Situ Hybridization
Extracellular Matrix
Sprague Dawley Rats
Albumins
Body Weight
Urine
RNA
Weights and Measures
Glucose
Control Groups
Serum

Keywords

  • Collagen IV
  • Diabetes
  • Diabetic nephropathy
  • Rat

Cite this

Altered kidney matrix gene expression in early stages of experimental diabetes. / Wu, K.; Setty, S.; Mauer, S. M.; Killen, P.; Nagase, H.; Michael, A. F.; Tsilibary, E. C.

In: Cells Tissues Organs, Vol. 158, No. 3, 01.01.1997, p. 155-165.

Research output: Contribution to journalArticle

Wu, K. ; Setty, S. ; Mauer, S. M. ; Killen, P. ; Nagase, H. ; Michael, A. F. ; Tsilibary, E. C. / Altered kidney matrix gene expression in early stages of experimental diabetes. In: Cells Tissues Organs. 1997 ; Vol. 158, No. 3. pp. 155-165.
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